Phase 3
Completed N=652
A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia
Source: ClinicalTrials.gov NCT03734016 ↗Enrolled (actual)
652
Serious AEs
56.8%
Results posted
Jul 2023
Primary outcomePrimary: Overall Response Rate (ORR) Assessed by the Investigator — 83.5; 74.2 percentage of participants — p=<0.0001
◆ Published Evidence
Established
83citations · ~14 / year
ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma.
Summary
This study is designed to compare the overall response rate of zanubrutinib versus ibrutinib in participants with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
Linked Publications (5)
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ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma.
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Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE.
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Acquired mutations in patients with relapsed/refractory CLL who progressed in the ALPINE study.
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Hypertension in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma in ALPINE: a secondary analysis.
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Zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: health-related quality of life in a subgroup of Chinese patients in the ALPINE trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Response Rate (ORR) Assessed by the Investigator |
83.5; 74.2 | <0.0001 sig |
| PRIMARY ORR Assessed by the Independent Review Committee (IRC) |
86.2; 75.7 | <0.0001 sig |
| SECONDARY Progression-free Survival (PFS) Assessed by the Investigator |
NA; 34.2 | <0.0001 sig |
| SECONDARY Progression-free Survival Assessed by the Independent Review Committee |
NA; 35.0 | <0.0001 sig |
| SECONDARY Percentage of Participants With Atrial Fibrillation or Atrial Flutter |
5.2; 13.3 | 0.0004 sig |
| SECONDARY Duration of Response Assessed by the Independent Review Committee |
NA; 33.9 | — |
| SECONDARY Duration of Response (DOR) Assessed by the Investigator |
NA; 33.9 | — |
| SECONDARY Time to Treatment Failure |
NA; NA | — |
| SECONDARY Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Independent Review Committee |
91.7; 83.1 | — |
| SECONDARY Rate of Partial Response With Lymphocytosis (PR-L) or Higher Assessed by the Investigator |
89.9; 82.5 | — |
| SECONDARY Overall Survival (OS) |
NA; NA | — |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL), Physical Functioning and Role Functioning Scores |
8.18; 5.18; 7.28; 5.93; 6.55; 4.73 | 0.0338 sig |
| SECONDARY Change From Baseline in EORTC QLQ-C30 Symptom Scales of Fatigue, Nausea and Vomiting, Pain, and Diarrhoea |
-12.54; -10.63; -11.13; -10.78; -1.21; -0.92 | 0.1778 |
| SECONDARY Change From Baseline in European Quality of Life 5-dimensions 5-levels Health Questionnaire (EQ-5D-5L) Visual Analog Scale (VAS) |
7.92; 3.44; 7.75; 3.92 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAE) |
322; 323; 172; 196 | — |
Eligibility Criteria
Key Inclusion Criteria
- Confirmed diagnosis of CLL or SLL that meets the 2008 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria
- CLL/SLL requiring treatment per 2008 IWCLL criteria
- Relapsed or refractory to at least 1 prior systemic therapy for CLL/SLL
- Measurable disease by computerized tomography (CT)/magnetic resonance imaging (MRI)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Life expectancy ≥ 6 months
- Adequate bone marrow function
- Adequate renal and hepatic function
Key Exclusion Criteria
- Known prolymphocytic leukemia or history of, or currently suspected, Richter's transformation
- Clinically significant cardiovascular disease.
- Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast
- History of severe bleeding disorder or history of spontaneous bleeding requiring blood transfusion or other medical intervention
- History of stroke or intracranial hemorrhage within 180 days before first dose of study drug
- Severe or debilitating pulmonary disease
- Active fungal, bacterial, and/or viral infection requiring systemic therapy
- Known central nervous system involvement by leukemia or lymphoma
- Known infection with HIV or active viral hepatitis B or C infection
- Moderate or severe hepatic impairment, ie, Child-Pugh class B or C
- Major surgery within 4 weeks of the first dose of study drug
- Prior treatment with a (Burton's Kinase) BTK inhibitor
- Toxicity from prior anticancer therapy that has not recovered to ≤ Grade 1
- Pregnant or lactating women
- Vaccination with a live vaccine within 35 days prior to the first dose of study drug
- Hypersensitivity to zanubrutinib, ibrutinib, or any of the other ingredients in either drug
- Concurrent participation in another therapeutic clinical trial
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT03734016) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.